This application claims priority from ROC Patent Application Serial Number 089113073 filed Jul. 1, 2000.
1. Technical Field
The present invention relates to a novel oral capsule preparation and the method for preparing the same.
2. Description of the Prior Art
For the drugs that are unstable, badly sensory or difficult to exhibit the efficacy, there are many problems in administration and manufacture. For example, those drugs are easily denatured, unable to fully exhibit the efficacy, or difficult to prepare. Therefore, it is necessary to develop a pharmaceutical formulation that can be easily produced with the improved bioavailability and enhanced stability.
In the prior art, for the drugs that are unstable, badly sensory or difficult to exhibit the efficacy, the powder modification or coating engineering process are need to provide the desired stability and curative effect when they are made as solid preparations. Therefore, the quality control of drugs is difficult due to different sources of raw materials or variation of the engineering techniques.
One aspect of the study in unstable drugs is anti-gastric ulcer drugs, wherein omeprazole is the most potent. According to the market survey and the evaluation of the developments of the drugs, the sale of omeprazole will stand the first in the world among the anti-gastric ulcer drugs.
Omeprazole (C12H19N3O3S), 5-methoxy-2(((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)sulfinyl)1H-benzimidazole, is an inhibitor of hydrogen potassium adenine nucleotidase, which is hardly soluble in water. Omeprazole is stable in the basic medium of a pH higher than 7 but is easily degraded or denatured in a neutral or acid medium (Pilbrant and Cederberg, Scand. J. Gastroenterology 1985; 20 (Supp. 108), pp. 113-120). For example, the half-life of omeprazole is only ten minutes in an aqueous solution at a pH less than 4 but is 14 hours in that solution at pH 7. Therefore, an oral dosage of omeprazole must be kept away from gastric juice to avoid the degradation before it reaches the small intestines.
Most omeprazole products are made from Astra Company. For example, ROC (Taiwan) Patent Application No. 76102439 provides an oral preparation of omeprazole, consisting of a core material (mixed with a basic compound or not) coated with one or more sublayer wherein the basic core contains omeprazole in combination with the buffered basic compound thereof such that the pH condition around omeprazole can be maintained in the range of 7-12. However, the cost is expensive because the process, time and control of the patented preparation are complicated.
ROC (Taiwan) Patent Application No. 78102957 discloses a solid pharmaceutical composition to increase the sustained time of omeprazole in stomach. However, there is no way to avoid a contact of omeprazole with gastric acid.
ROC (Taiwan) Patent Application No. 84104486 describes a process of preparing granulated preparations comprising the steps of: suspending omeprazole and an excipient in a suspension consisting of alcohol, water, ammonia water and binding agent; spraying the resulted suspension onto a core wherein the core is prepared from sugar, starch or microcrystal cellulose to obtain cored materials; adding the materials for granulation to the cored materials and then drying them. Omeprazole cannot be completely isolated from the acid environment during preparation such that the stability of omeprazole cannot be maintained well.
In the prior art, to prevent omeprazole from contacting with gastric juice, the omeprazole xe2x80x94containing cores are conventionally coated with enteric coatings. U.S. Pat. No. 2,540,979 provides an oral preparation with enteric coatings, wherein the enteric coatings are combined with a second and/or a first layer of water insoluble wax coating. However, a contact of omeprazole with acetate phthalate of the preparation reacts results in a degradation or color change of omeprazole.
Generally, an enteric coating is prepared from acid compounds. A direct or indirect contact of omeprazole with said acid compounds results in the denaturation and the loss of omeprazole. Karlsson, et. al. indicates that the stability of most omeprazole products, except Astra products is undesirable (Karlsson, et. al., 1996, International Pharmacy Journal, 10 (6); 210-213).
The invention provides an oral pharmaceutical preparation, which can be easily prepared, with an improved bioavailability and enhanced stability, which resolves the problems occurring in the prior art, such as unstability or difficulty in exhibiting the efficacy of omeprazole products.
One object of the invention is to provide an oral capsule preparation, which comprises a capsule prepared from a drug or the alkaline salt thereof, and oily compound or the alkaline salt thereof, an emulsifier, together with an enteric coating disposed on the capsule; wherein said emulsifier is a composition of C6-18 organic fatty acid and an organic amine or a polycarbon alcohol or the mixture thereof.
Another object of the invention is to provide a method of preparing the oral capsule preparation of the invention, comprising the steps of suspending a drug or the basic salt thereof in an emulsified fluid formed by mixing oil compounds or the basic salts thereof and an emulsifier, filling a capsule with the suspension, coating the outer surface of the capsule with an enteric coating, wherein the emulsifier is a composition of C6-18 organic fatty acid and an organic amine, or a polycarbon alcohol or the mixture thereof.